Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

Ivan Mercurio; Vincenzo Tragni; Francesco Busco; Anna De Grassi; Ciro Leonardo Pierri

In order to limit death rate and SARS-CoV-2 spread, it needs to develop a vaccine and to identify new small molecules able to prevent or treat COVID-19 complications, as well as to prepare new quick diagnosis kits, able to quantify the real number of people exposed to SARS-CoV-2. Among the main actors of SARS-CoV-2 infection the SARS-CoV-2 spike proteins, RNA dependent RNA polymerases and proteases deserve to be mentioned. Indeed, RNA dependent RNA polymerase has become one of the main targets of a nucleoside analog antiviral drug, the remdesivir, already used for reducing complications due to Ebola, Dengue and MERS-CoV infections (1) (2) (3) (4) (5) (6) . At the same time viral protease inhibitors (7) (8) (9) (10) are under investigation for their ability in preventing virus protein (with specific reference to spike proteins) cleavage (11) leading to the fusion of virus proteins with host cell membranes. Also anti-inflammatory antibodies/drugs in combination with anticoagulant molecules are under investigation for limiting coagulopathies (12) (13) (14) (15) and cytokine signaling impressively triggered by SARS-CoV-2 infection (16) (17) (18) (19) (20) . Finally, the same SARS-CoV-2 spike protein has become the most investigated target due to its ability in forming interactions with the human ACE2 receptor, causing fusion events that make possible for the virus to penetrate host human cells (21) (22) (23) .